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Research Article

A novel LC-QTOF-MS/MS method for trace level identification and quantification of potential genotoxic impurity, 5-Nitro-2-(propylthio)pyrimidine-4,6-diol in ticagrelor drug substance

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Pages 129-142 | Received 05 Jan 2024, Accepted 23 Mar 2024, Published online: 11 Apr 2024

References

  • James, S., Åkerblom, A., Cannon, C.P., Emanuelsson, H., Husted, S., Katus, H., Skene, A., Steg, P.G., Storey, R.F., Harrington, R., Becker, R., Wallentin, L. (2009). Comparison of ticagrelor, the first reversible oral P2Y12 receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. American Heart Journal. 157(4): 599-605. doi: 10.1016/j.ahj.2009.01.003
  • Storey, R.F., Angiolillo, D.J., Patil, S.B., Desai, B., Ecob, R., Husted, S., Emanuelsson, H., Cannon, C.P., Becker, R.C., Wallentin, L. (2010). Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes: The PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy. Journal of the American College of Cardiology. 56(18): 1456-1462. doi: 10.1016/j.jacc.2010.03.100
  • Angiolillo, D.J., Suryadevara, S., Capranzano, P., Bass, T.A. (2008). Prasugrel: A novel platelet ADP P2Y12 receptor antagonist. A review on its mechanism of action and clinical development. Expert Opinion on Pharmacotherapy. 9(16): 2893-2900. doi: 10.1517/14656566.9.16.2893
  • Dobesh, P.P., Oestreich, J.H. (2014). Ticagrelor: Pharmacokinetics, Pharma-codynamics, Clinical Efficacy and Safety. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 34(10): 1077-1090.
  • Zhou, D., Andersson, T.B., Grimm, S.W. (2011). In vitro evaluation of potential drug–drug interactions with ticagrelor: Cytochrome P450 reaction phenotyping, inhibition, induction, and differential kinetics. Drug Metabolism and Disposition: The Biological Fate of Chemicals. 39(4): 703-710. doi: 10.1124/dmd.110.037143
  • Tan, Q., Jiang, X., Huang, S., Zhang, T., Chen, L., Xie, S., Mo, E., Xu, J., Cai, S. (2017). The clinical efficacy and safety evaluation of ticagrelor for acute coronary syndrome in general ACS patients and diabetic patients: A systematic review and meta-analysis. PLOS ONE. 12(5): e0177872. doi: 10.1371/journal.pone.0177872
  • Fuller, R., Chavez, B. (2012). Ticagrelor (brilinta), an antiplatelet drug for acute coronary syndrome. P and T. 37(10): 562-568.
  • Wallentin, L., Becker, R.C., Budaj, A., Cannon, C.P., Emanuelsson, H., Held, C., Horrow, J., Husted, S., James, S., Katus, H., Mahaffey, K.W., Scirica, B. M., Skene, A., Steg, P.G., Storey, R.F., Harrington, R.A., PLATO Investigators, Freij, A., Thorsén, M. (2009). Ticagrelor versus clopidogrel in patients with acute coronary syndromes. New England Journal of Medicine. 361(11): 1045-1057. doi: 10.1056/NEJMoa0904327
  • Kabil, M.F., Dena, A.S.A., El-Sherbiny, I.M. (2022). Ticagrelor. In Profiles of Drug Substances, Excipients and Related Methodology. Academic Press. 47.
  • 5-Nitro-2-(Propylthio)Pyrimidine-4,6-Diol | C7H9N3O4S | CID 21696790. nih.gov; Retrieved October 27, 2023. PubChem.
  • 5-Nitro-2-(Propylthio)Pyrimidine-4,6-Diol-PubChem Substance. nih.gov, last access 28-Oct-2023. National Center for Biotechnology Information.
  • Shinde, G.B., Mahale, P.K., Padaki, S.A., Niphade, N.C., Toche, R.B., Mathad, V.T. (2015). An efficient and safe process for the preparation of ticagrelor, a platelet aggregation inhibitor via resin-NO2 catalyzed formation of triazole ring. SpringerPlus. 4(1): 493. doi: 10.1186/s40064-015-1299-6
  • Li, Z.H., Yang, D.X., Geng, P.F., Zhang, J., Wei, H.M., Hu, B., Guo, Q., Zhang, X.H., Guo, W.G., Zhao, B., Yu, B., Ma, L.Y., Liu, H.M. (2016). Design, synthesis and biological evaluation of [1, 2, 3] triazolo [4, 5-d] pyrimidine derivatives possessing a hydrazone moiety as antiproliferative agents. European Journal of Medicinal Chemistry. 124: 967-980. doi: 10.1016/j.ejmech.2016.10.022
  • Zhang, H., Liu, J., Zhang, L., Kong, L., Yao, H., Sun, H. (2012). Synthesis and biological evaluation of ticagrelor derivatives as novel antiplatelet agents. Bioorganic and Medicinal Chemistry Letters. 22(11): 3598-3602. doi: 10.1016/j.bmcl.2012.04.050
  • Bolt, H.M., Foth, H., Hengstler, J.G., Degen, G.H. (2004). Carcinogenicity categorization of chemicals New aspects to be considered in a European perspective. Toxicology Letters. 151(1): 29-41. doi: 10.1016/j.toxlet.2004.04.004
  • Jacobson-Kram, D., McGovern, T. (2007). Toxicological overview of impurities in pharma-ceutical products. Advanced Drug Delivery Reviews. 59(1): 38-42. doi: 10.1016/j.addr.2006.10.007
  • Amberg, A., Beilke, L., Bercu, J., Bower, D., Brigo, A., Cross, K.P., Custer, L., Dobo, K., Dowdy, E., Ford, K.A., Glowienke, S. (2016). Principles and procedures for implementation of ICH M7 recommended (Q) SAR analyses. Regulatory Toxicology and Pharmacology. 77: pp.13-24. doi: 10.1016/j.yrtph.2016.02.004
  • Guideline, ICH Harmonised. (2014). "Assessment and control of dna reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk M7." In Inter-national conference on harmonization of technical requirements for registration of pharmaceuticals for human use (ICH): Geneva.
  • Raman, N.V.V.S.S., Prasad, A.V.S.S., Ratna-kar Reddy, K. (2011). Strategies for the identification, control and determination of genotoxic impurities in drug substances: A pharmaceutical industry perspective. Journal of Pharmaceutical and Biomedical Analysis. 55(4): 662-667. doi: 10.1016/j.jpba.2010.11.039
  • Manchuri, K.M., Shaik, M.A., Gopireddy, V.S.R. (2022). A novel UHPLC-MS/MS method development and validation for identification and quantification of genotoxic impurity bis (2-chloroethyl) amine in aripiprazole drug substance. Chromatographia. 85(2): 137-146. doi: 10.1007/s10337-021-04123-x
  • Reddy, A.V.B., Jaafar, J., Umar, K., Majid, Z.A., Aris, A.B., Talib, J., Madhavi, G. (2015). Identification, control strategies, and analytical approaches for the determination of potential genotoxic impurities in pharmaceuticals: A comprehensive review. Journal of Separation Science. 38(5): 764-779. doi: 10.1002/jssc.201401143
  • Mullangi, S., Ravindhranath, K., Yarala, M.R., Panchakarla, R.K. (2023). A sensitive LC-MS/MS method for the determination of potential genotoxic impurities in cinnarizine. In Annales Pharmaceutiques Françaises. 81(1): 74-82. doi: 10.1016/j.pharma.2022.06.010
  • Shaik, M.A., Manchuri, K.M., Nayakanti, D. (2023). A novel UHPLC-MS/MS method for trace level identification and quantification of genotoxic impurity 2-(2-chloroethoxy) ethanol in quetiapine fumarate. Journal of Liquid Chromatography & Related Technologies. 46(16-20): 325-334. doi: 10.1080/10826076.2023.2276283
  • Moorthy, M.K., Ali, S.M., Reddy, G.V.S. (2022). A New Liquid chromatography Quadrupole Time Of Flight-tandem mass spectrometry Method Development and Validation for Identification and Ultra-Trace Level Quantification of genotoxic Impurity 1, 3-diacetoxy-2-(acetoxymethoxy) propane in valganciclovir hydrochloride Active Pha-rmaceutical Ingredient. Separation Science Plus. 5(3-4): 84-92. doi: 10.1002/sscp.202100076
  • Liu, D.Q., Sun, M., Kord, A.S. (2010). Recent advances in trace analysis of pharmaceutical genotoxic impurities. Journal of Pharmaceutical and Biomedical Analysis. 51(5): 999-1014. doi: 10.1016/j.jpba.2009.11.009
  • Ali, S.M., Moorthy, M.K., Devanna, N. (2023). A novel liquid chromatography with quadrupole time-of-flight-tandem mass spectroscopy method for ultra-trace level identification and quanti-fication of the genotoxic impurity 2, 6-diamino-5-nitropyrimidin-4 (3H)-one in valganciclovir hydrochloride. Biomedical Chromatography. p.e5805.
  • Moorthy, M.K., Ali, S.M., Reddy, G.V.S. (2022). Development and validation of LC–QTOF–MS/MS method for the identification and determination of low levels of a genotoxic impurity, 4, 6-dichloro-5-nitro-2-(propylthio) pyrimidine in ticagrelor API. Biomedical Chromatography. 36(4): e5336. doi: 10.1002/bmc.5336
  • Kumar, N., Devineni, S.R., Gajjala, P.R., Gupta, D.K., Bhat, S., Kumar, R., Dubey, S.K., Kumar, P. (2016). Four process-related potential new impurities in ticagrelor: Identification, isolation, characterization using HPLC, LC/ESI–MSn, NMR and their synthesis. Journal of Pharmaceutical and Biomedical Analysis. 120: 248-260. doi: 10.1016/j.jpba.2015.12.037
  • Kelemen, H., Hancu, G., Papp, L.A. (2019). Analytical methodologies for the determination of ticagrelor. Biomedical Chromatography. 33(7): e4528. doi: 10.1002/bmc.4528
  • Bueno, L.M., Manoel, J.W., Giordani, C.F.A., Mendez, A.S.L., Volpato, N.M., Schapoval, E.E.S., Steppe, M., Garcia, C.V. (2017). HPLC method for simultaneous analysis of ticagrelor and its organic impurities and identification of two major photodegradation products. European Journal of Pharmaceutical Sciences. 97: 22-29. doi: 10.1016/j.ejps.2016.11.004
  • Wingert, N.R., Ellwanger, J.B., Bueno, L.M., Gobetti, C., Garcia, C.V., Steppe, M., Schapoval, E.E.S. (2018). Application of Quality by Design to optimize a stability-indicating LC method for the determination of ticagrelor and its impurities. European Journal of Pharmaceutical Sciences. 118: 208-215. doi: 10.1016/j.ejps.2018.03.029
  • Kakde, R.B., Satone, D.D., Dongare, G., Chilbule, R., Malkhede, Y. (2017). Method development, validation and impurity profiling of ticagrelor by acid degradation method. International Journal of Pharm Tech Research. 10: 225-236.
  • Yaye, H.S., Secrétan, P.H., Henriet, T., Bernard, M., Amrani, F., Akrout, W., Do, B. (2015). Identification of the major degradation pathways of ticagrelor. Journal of Pharmaceutical and Biomedical Analysis. 105: 74-83. doi: 10.1016/j.jpba.2014.11.046
  • Kulkarni, P.R., Gajare, G.K. (2016). Develop-ment and validation of rp-hplc method for estimation of ticagrelor in bulk form. International Journal of Research in Pharmacy and Chemistry. 6(4): 733-737.
  • Tabassum, K., Sarvesh, R. (2017). Analytical method development and validation studies of ticagrelor tablets by RP-HPLC. International Journal of Applied Pharmaceutics. 9(4): 10-21. doi: 10.22159/ijap.2017v9i4.17440

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